Contents:

POTS Defined

Upright posture is a fundamental human activity requiring
rapid and effective circulatory and neurologic compensations in
order to maintain blood pressure and consciousness. The
orthostatic tachycardia syndrome is a disabling disease state
described at least since 1940 and is the most common reason for
referral for chronic orthostatic intolerance. Patients are often
unable to hold jobs or attend schools. Yet, our understanding of
its pathophysiology remains incomplete. An operational definition
of the syndrome (often denoted by the acronym POTS for postural
orthostatic tachycardia syndrome) includes symptoms of
orthostatic intolerance associated with an increase in heart rate
from the supine to upright position of more than 30 beats per
minute or to a heart rate greater than 120 beats per minute
within 10 minutes of head-up tilt (HUT). An exaggerated increase
in heart rate, often accompanied by hypotension in association
with dizziness, nausea, palpitations, heat and fatigue in the
upright position has been described under other names including
the hyperadrenergic syndrome of Streeten, idiopathic hypovolemia
of Fouad et al, and most recently the postural orthostatic
syndrome of Low et al. POTS is common, affecting an undisclosed
number of patients mostly in the age range of 12 to 50 years,
mostly female (approximately 80%), often with onset following a
viral infection or other inflammatory condition. There is an as
yet undetermined but increasing apparent prevalence in children
and adolescents. Resting tachycardia is common. Symptoms of
anxiety may proliferate and appear to be autonomically mediated
in many cases; there is also overlap with anxiety/panic disorder.

Patterns of heart rate and blood pressure variation are shown
in the figure and are from
our paper which was the first to directly discuss POTS in the
pediatric population.

POTS and CFS

POTS has been proposed as a mechanism for symptoms of the
Chronic Fatigue Syndrome in a series of adult patients. POTS and
CFS may share a common pathophysiology particularly in the young
. Recently, a review of patients with delayed orthostatic
hypotension (delayed POTS) demonstrated a high degree of
association with chronic fatigue. Our preliminary data have shown
that POTS physiology underlies orthostatic intolerance in the
large majority of adolescents with the chronic
fatigue syndrome (CFS). In those patients we
demonstrated loss of heart rate variability consistent with
vagal withdrawal, increased blood pressure variability consistent
with enhanced modulation of sympathetic tone, and impaired
baroreflex with a phase shift causing wide blood pressure swings
uncompensated by compensatory HR changes. Preliminary
vascular data suggest that these autonomic findings are
associated with changes in arterial and venous properties of the
lower limbs during orthostasis causing fluid collection in excess
of ordinary "pooling" observed in control patients.

Pathophysiology of POTS

Pooling in the lower body due to
gravity is believed to cause the findings. Indeed pooling changes
were found in early work and may be quite striking. Maneuvers to
increase effective blood volume such as acute saline loading and
lower body compression with pressure suits will reverse symptoms
and signs temporarily.

The literature contains a number of potential explanations for
abnormal venous pooling and fluid collection in POTS including
impaired innervation of the veins or in their response to
sympathetic stimulation. One such explanation favors an autonomic
neuropathy that predominantly affects the lower extremities.
Alpha1-adrenergic denervation hypersensitivity results. A second
explanation invokes decreased alpha1- receptor sensitivity; a
third, beta 1-receptor supersensitivity, a fourth altered
venoconstriction, while a fifth suggests increased capillary
filtration as an explanation. However, alpha 1-adrenergic control
of venous filling in response to baroreflex stimulation during
orthostasis is important only in skin and splanchnic circulations
in humans while involvement of skeletal muscle alpha 1-receptors
remain controversial. Beta-adrenergic effects may also alter
venous filling, but only indirectly through arterial vasoactivity
and this mechanism may be most important during exogenous beta-agonist
administration (isoproterenol) or during endogenous epinephrine
release later during HUT. It is uncertain how important active
venoconstriction is to the orthostatic response. Finally, venous
capacitance properties in POTS could be abnormal because of
altered vascular structure, altered muscle tone or both.

Pooling

Normal

We noted a high incidence of acral findings in CFS and POTS
patients during HUT. Patients had swelling of the dependent lower
extremities with purplish discoloration of the dorsum of the foot
and ankle. The figure shows early
published data depicting percent change in mid-calf circumference
from baseline prior to tilt until the end of tilt just prior to
being placed supine. The data suggest a significantly greater
percent increase in circumference in POTS patients compared with
syncope patients or control subjects as the result of increased
pooling. Clinically, there was coolness with livedo reticularis
suggesting arterial malperfusion, venous dysfunction or both.